HIV-associated Neurocognitive Disorders Research Articles

34 Variability in RBANS Performance and Neurocognitive Impairment in Older Adults with Cognitive Concerns

Objective:Risk factors that contribute to brain pathology and cognitive decline among older adults include demographic factors (e.g., age, educational attainment), genetic factors, health factors, and depression (Plassman et al., 2010). Variability within an individual’s performance across cognitive tasks is referred to as dispersion (Hultsch et al., 2002), which appears sensitive to subtle cognitive impairments associated with neurodegenerative pathology in older adults (Bangen et al., 2019; Kälin et al., 2014). Thaler and colleagues (2015) found that dispersion across domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was a useful indicator of cognitive changes associated with cardiovascular disease and mortality. Also, research by Manning and colleagues (2021) found that elevated ratings of depression and anxiety in older adults was associated with greater dispersion across neuropsychological testing. The present study aimed to replicate findings that greater dispersion in neuropsychological performance is associated with impaired neurocognitive performance and greater self-reported depression among older adults who present for neuropsychological evaluation with cognitive concerns.Participants and Methods:Neuropsychological testing data was obtained from a university hospital. Chart reviews were conducted on 369 participants who met initial criteria (60 years or older with testing data from the RBANS Form A, Wechsler Test of Adult Reading, and Geriatric Depression Scale [GDS]). Retrospective analyses were conducted on a final sample of 293 participants from 60 to 94 years old (Mage = 74.41, SDage = 7.43; 179 females, 114 males). Diagnoses were used for group comparisons between cognitively intact individuals with subjective cognitive complaints (SCC, n = 49), persons with Mild Neurocognitive Disorder (mND, n =137), and persons with Major Neurocognitive Disorder (MND, n = 107).Results:As expected, results indicated that higher dispersion was related to lower Total RBANS Scores (r = -0.54, p < .001) and significant differences across diagnostic groupings (F(2, 289) = 29.19, p < 0.001; SCC, mND, MND) indicated that variability in performance was an indicator of greater neurocognitive impairment. Contrary to expectations, greater dispersion was very weakly associated with lower reported depressive symptomatology (r = -0.13, p = 0.03). A three-stage hierarchical linear regression was conducted with the RBANS Coefficient of Variation (CoV) as the dependent variable and three predictor variables (Age, Total RBANS, Total GDS). The regression analysis results indicated that age was not a significant predictor, but both Total RBANS and GDS Scores were. The most important predictor was Total RBANS Scores which uniquely explained 21% of the variation in dispersion.Conclusions:This study adds to the current literature regarding the clinical utility of dispersion in neuropsychological performance as an indicator of early and subtle neurocognitive impairment. Depressive symptom reporting was expected to help predict the degree of variability, but this factor was only weakly associated with the RBANS CoV.Limitations of this study include its retrospective use of archival data and the restricted range on some variables of interest. Further research is needed to examine the relative utility of different measures of dispersion and why increased cognitive performance variability is related to neurocognitive impairment and decline.

80 Processing Speed Mediates the Association between Executive Functioning and Adaptive Functioning Among Older Adults

Objective:Cognitive decline is expected in normative aging (Cabeza et al., 2018; Salthouse, 2019), which can lead to impairments in adaptive functioning (Yam et al., 2014). Several cognitive domains have been associated with adaptive functioning in older adult samples, including processing speed and executive functioning (e.g., Nguyen et al., 2019; Vaughn & Giovanello, 2010). A recent study examining a mixed clinical sample of older adults demonstrated that processing speed was more predictive of functional decline than other cognitive domains, including aspects of executive functioning (Roye et al., 2022). Therefore, this study attempts to build on previous findings by further examining the relationships between processing speed, adaptive functioning, and executive functioning. Specifically, it investigated the extent to which processing speed mediated the associations between executive functioning and adaptive functioning.Participants and Methods:Participants (N = 239) were selected from a clinical database of neuropsychological evaluations. Inclusion criteria were age 60+ (M = 74.0, SD = 6.9) and completion of relevant study measures. Participants were majority White (93%) women (53.1%). Three cognitive diagnosis groups were coded: No Diagnosis (N = 82), Mild Neurocognitive Disorder (NCD; N = 78), and Major NCD (N = 79). The Texas Functional Living Scale (TFLS) was used as a performance-based measure of adaptive functioning. Processing speed was measured using the Coding subtest from the Repeatable Battery for the Assessment of Neuropsychological Status. Executive functioning performance was quantified using part B of the Trail Making Test, Controlled Oral Word Association Test, and Similarities and Matrix Reasoning subtests from the WAIS-IV and WASI-II. Mediation models included age and years of education as covariates and indirect effects were assessed with bootstrapped confidence intervals (Hayes, 2020).Results:Processing speed mediated all measures of executive functioning. The pattern was consistent for all executive functioning measures such that poorer executive functioning was associated with poorer processing speed, which was subsequently associated with poorer adaptive functioning. Direct effects were significant for all models (ps < .03), suggesting that executive functioning maintained unique associations with adaptive functioning. Follow-up analyses indicated no evidence for moderation of the mediation models based on diagnostic group.Conclusions:These results highlight the importance of processing speed in understanding real-world implications of pathological and non-pathological cognitive aging. Processing speed mediated all relationships between executive functioning and adaptive functioning. There was no evidence for moderation of these effects, supporting generalizability regardless of neurocognitive disorder and etiologic subtype. Further investigation is warranted into the importance of processing speed in explaining associations of other cognitive domains with adaptive functioning.

55 Psychometric Properties of the Verbal Series Attention Test: Preliminary Findings

Objective:To investigate the latent factor structure and construct validity of the Verbal Series Attention Test (VSAT) across clinical patient populations.Participants and Methods:Participants included a consecutive series of clinical patients presenting with a primary memory complaint. Each patient underwent a comprehensive neuropsychological assessment and provided informed consent to allow their clinical data to be used for research. Groups formed included 1) No Neurocognitive Disorder [NoND, N=262, mean age=68.8, mean education=16.2, mean MMSE=28.3], 2) Mild Neurocognitive Disorder [MildND, N=337, mean age=72.3, mean education=15.4, mean MMSE=28.7], and 3)Major Neurocognitive Disorder [MajorND, N=524, mean age=76.5, mean education=14.5, mean MMSE=19.0] with etiologies including suspected Alzheimer’s disease and/or vascular pathology. Latent factors were investigated using exploratory factor analysis (EFA).Results:EFA was conducted using SAS 9.4 software and the promax (oblique) rotation to reveal the latent factors of the eight timed items of the VSAT in each of the three clinical groups. The structure was essentially identical in all three groups with two primary factors consistently emerging identified as 1-Complex Attention and 2-Simple Attention. Each factor had four items loading with a correlation range of > 0.37 x < 0.92. The internal consistency (Cronbach’s alpha) for the VSAT total score in each group was excellent (NoND a=0.83, MildND a=0.81, and MajorND a=0.84). To investigate construct validity, the VSAT items were entered into factor analysis with measures of attention and executive function (i.e., Digit Span [forward, backward, sequence], Trail Making Test A & B, semantic fluency (animals), Controlled Oral Word Association Test [COWAT, FAS]). All three patient groups were combined (N=950) given the VSAT’s consistent factor structure. Using the same EFA procedure as before, two main factors emerged with the VSAT Complex Attention variables loading on a general complex attention/working memory factor including Trails B, semantic fluency, and Digit Span subtests. The VSAT Simple Attention items loaded on a general attention factor with the VSAT Simple Attention variables and Trails A. COWAT did not load significantly on either factor.Conclusions:The latent factor structure of the VSAT was consistent across patient populations with excellent internal consistency in each clinical group. The Complex and Simple Attention factors of the VSAT loaded on factors with similar variables identifying the anticipated latent factor structure demonstrating the construct validity of the VSAT across a wide spectrum of cognitive impairment in patients with primary memory complaints ranging from NoND to MajorND. This supports the use of the VSAT in patients across neurocognitive severity. Future studies will further explore additional psychometric properties of this instrument.

30 Socially Responsible Neuropsychology (SRN) in Action: The Role of Neuropsychology in Migraine Care Among Bilingual Latina/o Patients

Objective:Migraine is one of the leading causes of disability worldwide and a recognized contributor to health disparities with public health implications. Although migraine is a highly prevalent neurological condition, research on the cognitive manifestations of migraines is inconsistent. Studies have confirmed neurocognitive compromise during the presence of a migraine attack, with it’s onset and frequency being associated with greater cognitive decline. Research on the cognitive implications of migraines in underserved communities is scarce. The American Migraine Prevalence and Prevention Study (2015) found that the prevalence of chronic migraines was the highest amongst Hispanic females compared to White females. Latina/os are 50% less likely to receive a migraine diagnosis and adequate headache medication when compared to non-Hispanic White patients. Latina women were more likely to report somatic symptoms than White and African American participants (F=8.96; p>0.001) (Liefland et al., 2014). Somatoform disorders are often diagnosed amongst Latina/os to account for medical unexplained symptoms, and if misdiagnosed can be stigmatizing and detrimental to treatment. We illustrate the critical role that neuropsychologists play by utilizing Socially Responsible Neuropsychology (SRN), a theoretical framework that promotes equitable and precise neuropsychological care to reduce misdiagnosis, elucidate cognitive implications, and address the complex medical needs of Latina/o/ patients. Given the limited literature on migraines and neurocognitive functioning, our objective is to present two case studies to illustrate the neuropsychological implications among bilingual Latina/o with chronic migraines.Participants and Methods:Two highly educated Latina/o women, ages 39 and 41 years old, with chronic migraines, cognitive decline, diagnoses and a history of somatization symptoms. The onset of symptoms was gradual, worsening in intensity and frequency, along with notable motor symptoms (e.g., paralysis, weakness, numbness, bilateral tremors), photophobia, and phonophobia. Their cognitive complaints were conceptualized as part of a somatoform presentation by their providers.Results:The SRN model guided clinical decision-making to establish reliable normative anchors to identify relative impairment compared to premorbid estimates. Testing was completed in English after establishing language dominance via English and Spanish measures of verbal fluency. Cognitive profiles identified declines in attention, processing speed, language, perceptual reasoning, visual memory, executive functioning, motor functioning, and notable decline in their functioning over several years. The neuropsychological profile discounted the presence of a somatoform disorder. One case was diagnosed with an Unspecified Mild Neurocognitive Disorder, while the other case met criteria for a Major Neurocognitive Disorder due to Multiple Etiologies (i.e., vascular contribution, migraines, history of other contributions- choking episode).Conclusions:Given the decline in each profile, it was hypothesized that the patients’ utilization of compensatory strategies and higher education may have masked the onset of symptoms. These complex cases highlight the need for comprehensive neuropsychological evaluations that are culturally and linguistically responsive to boost the sensitivity of accurate diagnosis. The ability to objectively capture neurocognitive decline offers a unique opportunity to enhance treatment, which would have otherwise remained undetected and untreated. The SRN model enhanced diagnostic considerations, treatment planning, and allowed for advocacy strategies to improve the quality of life, and access to culturally/linguistically appropriate resources.

74 Adherence to Behavioral Interventions is Associated with a Change in Participant Adjustment in a Sample of aMCI Patients

Objective:Behavioral interventions are a non-pharmacological treatment that shows improvement in the everyday functioning of people with Mild Cognitive Impairment (MCI). Multiple studies have focused on examining factors that can reduce or enhance adherence to behavioral interventions. However, few studies use adherence as a predictor of functional changes. The goal of this study was to analyze the association between adherence, age, and education in factor score changes of participant impairment, participant adjustment, and partner adjustment in a sample of participants with amnestic MCI (aMCI) and their study partners.Participants and Methods:We included fifty-two dyads of a person with aMCI and their study partner with intervention data at baseline and 24-week follow-up from the Physical Exercise and Cognitive Engagement Outcomes for Mild Neurocognitive Disorder (PEACEOFMND) study. At baseline, participants were randomized to one of three behavioral interventions: computerized cognitive training (BrainHQ; n=19), yoga (n=15), or wellness education (n=18). Factors were established from a larger clinical sample that used the same measures as PEACEOFMND. The three-factor latent structure was constructed as the following: 1) participant adjustment combined scores of the Center for Epidemiologic Studies Depression Scale (CES-D), Quality of Life in Alzheimer’s Disease (QoL-AD), and Self-Efficacy for managing MCI scales; 2) partner adjustment included study partner’s scores in CES-D, QoLAD and Caregiving Competence and Mastery Components (CCMC) of the Pearlin scales; 3) participant impairment included participant’s scores in E-Cog memory domain, and study partner’s scores in the Functional Activity Questionnaire (FAQ) and Zarit Burden Interview. We calculated factor changes by obtaining the difference between factor scores at follow-up and baseline. Bayesian correlation analysis was performed to investigate the association between age, education, adherence to the combined behavioral interventions, participant adjustment, participant impairment, and partner adjustment.Results:The Bayesian correlation results showed moderate evidence (BF10=6.8, Pearson’s r=0.38) supporting a positive correlation between adherence and change in participant adjustment. Additionally, there was moderate evidence (BF10=2.18, Pearson’s r=0.32) supporting a positive correlation between change in participant impairment and participant level of education as well as participant age and change in partner adjustment (BF10=2.8, Pearson’s r=0.33).Conclusions:Bayesian correlations replicated results from previous analysis using a traditional method, showing that increased adherence to combined behavioral interventions is associated with an increase in participant’s quality of life, self-efficacy, and better mood. Thus, commitment to behavioral intervention completion in aMCI participants is related to overall participant adjustment.

Changes in Cerebrospinal Fluid, Liver and Intima-media-thickness Biomarkers in Patients with HIV-associated Neurocognitive Disorders Randomized to a Less Neurotoxic Treatment Regimen

The prevalence of neurocognitive impairment in people living with HIV is estimated between 30 and 50%. The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. Aim of the study was to measure the change in CSF biomarkers, Fibroscan and IMT measurements in PLWH with HAND randomized to a less neurotoxic regimen, or continuing their treatment. Adult patients with HAND were screened and enrolled if presenting no major resistance associated mutations, no HIV viral replication, not on efavirenz or darunavir, with R5-tropic HIV and without major confounding conditions. Lumbar puncture, IMT and Fibroscan measurements were performed. After 1:1 randomization to a less neurotoxic regimen consisting of darunavir/cobicistat plus emtricitabine plus maraviroc, or mantaining actual care, tests were repeated after 24 weeks: CSF biomarkes (HIV RNA, tau, p-tau, Beta-amyloid1-42, S100Beta and neopterin) were included. Non-parametric tests (Mann–Whitney and Wilcoxon’s) were used. 28 participants completed the study. Male and European ancestry were prevalent; median age was 55 years (51–60). All patients were virally suppressed; median CD4 + count was 626 cell/uL (469–772). Baseline characteristics were similar between the study arms. A significant decrease in CSF p-tau and an increase in CSF neopterin and NFL were observed. We observed a significant reduction in liver stiffness at W24. Despite a small sample size we observed changes in neuromarkers and in hepatic stiffness in patients randomized to the experimental arm. We observed changes in CSF biomarkers (lower phosphorylated-tau and higher neopterin and NFL) that need to be replicated in large cohorts. Subclinical neurotoxicity may be observed in patients with HAND and warrants prospective studies.Graphical

Analysis of posterior reversible encephalopathy syndrome in a patient with HIV/AIDS and schistosomiasis

We present the case of a patient from South Africa who had HIV and posterior reversible encephalopathy syndrome. Despite the fact that schistosomiasis and PRES have common pathophysiological molecular processes, there have been no earlier descriptions relating the two illnesses. This lecture emphasises the importance of additional inquiry into this probable link. In endemic locations, the interaction between HIV and schistosomiasis remains a significant research topic.

How does apathy impact exploration-exploitation decision-making in older patients with neurocognitive disorders?

Apathy is a pervasive clinical syndrome in neurocognitive disorders, characterized by a quantitative reduction in goal-directed behaviors. The brain structures involved in the physiopathology of apathy have also been connected to the brain structures involved in probabilistic reward learning in the exploration-exploitation dilemma. This dilemma in question involves the challenge of selecting between a familiar option with a more predictable outcome, and another option whose outcome is uncertain and may yield potentially greater rewards compared to the known option. The aim of this study was to combine experimental procedures and computational modeling to examine whether, in older adults with mild neurocognitive disorders, apathy affects performance in the exploration-exploitation dilemma. Through using a four-armed bandit reinforcement-learning task, we showed that apathetic older adults explored more and performed worse than non-apathetic subjects. Moreover, the mental flexibility assessed by the Trail-making test-B was negatively associated with the percentage of exploration. These results suggest that apathy is characterized by an increased explorative behavior and inefficient decision-making, possibly due to weak mental flexibility to switch toward the exploitation of the more rewarding options. Apathetic participants also took longer to make a choice and failed more often to respond in the allotted time, which could reflect the difficulties in action initiation and selection. In conclusion, the present results suggest that apathy in participants with neurocognitive disorders is associated with specific disturbances in the exploration-exploitation trade-off and sheds light on the disturbances in reward processing in patients with apathy.

Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins.

Although the widespread use of antiretroviral therapy (ART) has prolonged the life span of people living with HIV (PLWH), the incidence of HIV-associated neurocognitive disorders (HAND) in PLWH is also gradually increasing, seriously affecting the quality of life for PLWH. However, the pathogenesis of HAND has not been elucidated, which leaves HAND without effective treatment. HIV protein transactivator of transcription (Tat), as an important regulatory protein, is crucial in the pathogenesis of HAND, and its mechanism of HAND has received widespread attention. The blood-brain barrier (BBB) and its cellular component brain microvascular endothelial cells (BMVECs) play a necessary role in protecting the central nervous system (CNS), and their damage associated with Tat is a potential therapeutic target of HAND. In this review, we will study the Tat-mediated damage mechanism of the BBB andpresent multiple lines of evidence related to BMVEC damage caused by Tat.

Current clinical presentations of AIDS dementia in a tropical environment: study of 26 observations in the neurology department of the University Hospital of Conakry

IntroductionIn sub-Saharan Africa (SSA), the clinical and progressive diagnostic certainty of AIDS dementia is difficult to establish due to under-medicalization and delays in consultation and especially the diversity of etiologies of demented states.Material and methodsWe carried out a retrospective study of 196 patients hospitalized for dementia syndrome between 2016 and 2021 in the neurology department of the University Hospital of Conakry.The criteria labeled in this study are those retained by the DSM-IV and the classification of the American Academy of Neurology (AAN) developed in accordance with the WHO.ResultsHIV etiology was identified in patients aged 44–67 years (17 women and 19 men). The clinical picture was dominated by severe cognitive disorders, slowed ideation, memory disorders and reduced motor skills associated with personality changes. Neurological examination revealed dysphoric disorders in most patients, sphincter abnormalities in 13 cases and labio-lingual tremor in 11 cases. Diagnosis was based on positive serological tests for HIV1 antibodies (25 cases) and HIV2 antibodies (1 case) using the Elisa and Western blot techniques, and the presence of discretely hypercellular CSF. Magnetic resonance imaging contributed to the diagnosis, showing diffuse white matter abnormalities with hyper signals on T2-weighted or FLAIR sequences.ConclusionThis study shows a non-stereotype clinical picture of AIDS dementia requiring a differential diagnosis with other infectious dementias. These results are important for the therapeutic and prognostic discussion.

Alterations in glutamate, arginine, and energy metabolism characterize cerebrospinal fluid and plasma metabolome of persons with HIV-associated dementia.

HIV-associated dementia (HAD) is the most severe clinical expression of HIV-mediated neuropathology, and the processes underlying its development remain poorly understood. We aimed to exploit high-dimensional metabolic profiling to gain insights into the pathological mechanisms associated to HAD. In this cross-sectional study, we utilized metabolomics to profile matched cerebrospinal fluid (CSF) and plasma samples of HAD individuals ( n = 20) compared with neurologically asymptomatic people with HIV (ASYM, n = 20) and healthy controls (NEG, n = 20). Identification of plasma and CSF metabolites was performed by liquid-chromatography or gas-chromatography following a validated experimental pipeline. The resulting metabolic profiles were analyzed by machine-learning algorithms, and altered pathways were identified by comparison with KEGG pathway database. In CSF, HAD patients displayed an imbalance in glutamine/glutamate ratio, decreased levels of isocitrate and arginine, and increased oxidative stress when compared with ASYM or NEG. These changes were confirmed in matched plasma samples, which in addition revealed an accumulation of eicosanoids and unsaturated fatty acids in HAD individuals. Pathway analysis in both biological fluids suggested that alterations in several metabolic processes, including protein biosynthesis, glutamate and arginine metabolism, and energy metabolism, in association to a perturbed eicosanoid metabolism in plasma, may represent the metabolic signature associated to HAD. These findings show that HAD may be associated with metabolic modifications in CSF and plasma. These preliminary data may be useful to identify novel metabolic biomarkers and therapeutic targets in HIV-associated neurological impairment.

Influence of HIV infection on cognition and overall intelligence in HIV-infected individuals: advances and perspectives.

It is now well understood that HIV-positive individuals, even those under effective ART, tend to develop a spectrum of cognitive, motor, and/or mood conditions which are contemporarily referred to as HIV-associated neurocognitive disorder (HAND), and which is directly related to HIV-1 infection and HIV-1 replication in the central nervous system (CNS). As HAND is known to induce difficulties associated with attention, concentration, and memory, it is thus legitimate and pertinent to speculate upon the possibility that HIV infection may well influence human cognition and intelligence. We therefore propose herein to review the concept of intelligence, the concept of cells of intelligence, the influence of HIV on these particular cells, and the evidence pointing to differences in observed intelligence quotient (IQ) scores between HIV-positive and HIV-negative individuals. Additionally, cumulative research evidence continues to draw attention to the influence of the gut on human intelligence. Up to now, although it is known that HIV infection profoundly alters both the composition and diversity of the gut microbiota and the structural integrity of the gut, the influence of the gut on intelligence in the context of HIV infection remains poorly described. As such, we also provide herein a review of the different ways in which HIV may influence human intelligence via the gut-brain axis. Finally, we provide a discourse on perspectives related to HIV and human intelligence which may assist in generating more robust evidence with respect to this issue in future studies. Our aim is to provide insightful knowledge for the identification of novel areas of investigation, in order to reveal and explain some of the enigmas related to HIV infection.

The Efficacy of Cognitive Training on Neuropsychological Outcomes in Mild Cognitive Impairment: A Meta-Analysis.

Mild cognitive impairment (MCI) or mild neurocognitive disorder is an intermediate stage of cognitive impairment between normal cognitive aging and dementia. Given the absence of effective pharmacological treatments for MCI, increasing numbers of studies are attempting to understand how cognitive training (CT) could benefit MCI. This meta-analysis aims to update and assess the efficacy of CT on specific neuropsychological test performance (global cognitive functioning, short-term verbal memory, long-term verbal memory, generativity, working memory, and visuospatial abilities) in individuals diagnosed with MCI, as compared to MCI control groups. After searching electronic databases for randomized controlled trials, 31 studies were found including 2496 participants. Results showed that CT significantly improved global cognitive functioning, short-term and long-term verbal memory, generativity, working memory, and visuospatial abilities. However, no significant effects were observed for shifting, abstraction ability/concept formation, processing speed, and language. The mode of CT had a moderating effect on abstraction ability/concept formation. The findings provide specific insights into the cognitive functions influenced by CT and guide the development of tailored interventions for MCI. While CT holds promise, further research is needed to address certain cognitive deficits and assess long-term effects on dementia progression.

The Impact of Neurotransmitters on the Neurobiology of Neurodegenerative Diseases.

Neurodegenerative diseases affect millions of people worldwide. Neurodegenerative diseases result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction of these brain and nerve functions is associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and motor neuron disease. In addition to these, 50% of people living with HIV develop a spectrum of cognitive, motor, and/or mood problems collectively referred to as HIV-Associated Neurocognitive Disorders (HAND) despite the widespread use of a combination of antiretroviral therapies. Neuroinflammation and neurotransmitter systems have a pathological correlation and play a critical role in developing neurodegenerative diseases. Each of these diseases has a unique pattern of dysregulation of the neurotransmitter system, which has been attributed to different forms of cell-specific neuronal loss. In this review, we will focus on a discussion of the regulation of dopaminergic and cholinergic systems, which are more commonly disturbed in neurodegenerative disorders. Additionally, we will provide evidence for the hypothesis that disturbances in neurotransmission contribute to the neuronal loss observed in neurodegenerative disorders. Further, we will highlight the critical role of dopamine as a mediator of neuronal injury and loss in the context of NeuroHIV. This review will highlight the need to further investigate neurotransmission systems for their role in the etiology of neurodegenerative disorders.

Epidemiology of neurocognitive disorders in adults from urban-marginalized areas: a door-to-door population-based study in Puente Piedra, Lima, Peru.

In Latin America (LA), the prevalence of dementia is expected to triple to 150 million people by 2050. The 2020 Lancet Commission report identified several modifiable dementia risk factors, yet few social and environmental factors, most relevant to vulnerable regions of LA, were highlighted in this report. We sought to assess the epidemiology of neurocognitive disorders (NCD) in Puente Piedra, one of the most socially and economically vulnerable districts of Lima, the capital of Peru. This was a cross-sectional door-to-door observational study that used two-stage household sampling. One young adult (30-59 years) and one older adult (>60 years) per household were enrolled. We collected demographic, clinical, and neurocognitive data. Addenbrooke's Cognitive Examination (young adults) and the RUDAS-PE (older adults) were used, classifying participants as cognitively normal, possible mild NCD, or possible major NCD. We enrolled 247 participants (median age 46 years; 67% female). One-fourth had not completed secondary school and more than 50% completed only secondary school. Most participants were housewives (46%) and 21% did not have health insurance. The overall prevalence of possible NCD was 30% (25.6 and 41.8% among younger adults and older adults, respectively). Among younger adults, those ages 55-59 years more frequently had NCD (70%) compared to younger age ranges. Among older adults, only 3 subjects (4.5%) had major NCD. We found a high frequency of possible NCDs in a socially and economically vulnerable community in Lima, Peru, with younger adults showing levels of NCD higher than expected. Our findings support the need for health systems to incorporate cognitive screenings programs for NCD in younger ages. Future research on NCD would include younger populations, particularly in vulnerable communities.

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.

Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); however, PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH. Chronic use of these substances disrupts brain function, structure, and cognition. PLWH with SUD have poor health outcomes driven by complex interactions between biological, neurocognitive, and social factors. Here we review the effects of comorbid HIV and psychostimulant use disorders by discussing the distinct and common effects of HIV and chronic cocaine and methamphetamine use on behavioral and neurological impairments using evidence from rodent models of HIV-associated neurocognitive impairments (Tat or gp120 protein expression) and clinical studies. We also provide a biopsychosocial perspective by discussing behavioral impairment in differentially impacted social groups and proposing interventions at both patient and population levels.

H - 69 Making Diagnostic Decisions Using Linguistically Congruent Neuropsychological Assessment in a Monolingual Low Education Latino: a Single Case.

As life expectancy and Latino populations increase in the United States, it is important to provide linguistically congruent neuropsychological assessments to assist in the treatment and diagnosis of neurodegenerative processes. This case used a linguistically congruent evaluation and appropriate norms in a 72-year-old Latin male with low education, to inform treatment recommendations. A 72-year-old Latin male with five years of education was referred by his neurologist in the context of cognitive, behavioral, and functional decline over the past several years. He was educated outside of the United States, in a Spanish-speaking country, and speaks limited English. Therefore, testing was administered in Spanish. All test data were compared to other Spanish-speaking clinical patients with low education levels from his country of origin when available (11 articles). Overall given the evidence, he was diagnosed with Mild Neurocognitive Disorder due to Multiple Etiologies, with behavioral disturbance. His profile revealed weaknesses in verbal learning and memory, attention, and psychomotor processing speed. However, when compared to non-corrected norms, he performed significantly different (at least 1 SD) across several measures. Using a linguistically congruent evaluation, in addition to a compilation of age and education-corrected norms, we came to a diagnostic conclusion of a Mild Neurocognitive Disorder. If the normative data not been corrected for age and education, his impairments in visuospatial abilities and attention would have been inflated. As the Latino population continues to age, it becomes increasingly important to develop ways to assess this population appropriately.

H - 28 Assessment Following Acquired Injury to the Bilingual Brain: La Importancia De Los Determinantes Sociales De La Salud.

Given the growth of Latine populations in the U.S., variations in language fluency, educational attainment, quality of academic exposure, and access to medical care are essential social determinants of health to consider when assessing language in first generation immigrants, as illustrated through the following case study. A 17-year-old, Spanish-dominant, right-handed, Latina female with right frontoparietal stroke in the setting of arteriovenous malformation (AVM) was referred for neuropsychological evaluation one year following two consecutive gamma knife procedures. Complications included seizures (well-managed with Vimpat) and cerebral edema (treated with prolonged, high-dose Dexamethasone) followed by iatrogenic Cushing's syndrome. Brain MRI/CT were consistent with ruptured right frontoparietal AVM and vasogenic edema. Patient was a sequential language learner; education was received in Spanish until immigration from Colombia to the U.S. two years prior to injury. Parents completed higher education in Colombia. Consistent with stroke location/associated treatments, results indicated a mild neurocognitive disorder with deficits in cognitive efficiency, executive functioning (particularly on visual-based tasks), and memory. Academic skills also aligned with AVM (word reading: high average; reading comprehension: average; calculation: below average). Interestingly, even in the context of high parental education and dual language learner status, personal weaknesses in native language were identified (one-word expression: low average; semantic verbal fluency: below average). Integrating sociocultural demographic factors into the neuropsychological evaluation process supports a culturally-informed assessment approach and is imperative for practice with multilingual speakers. In this case, language concerns may have indicated premorbid weakness or right-sided/bilateral hemispheric language involvement, warranting follow-up fMRI/language mapping prior to further intervention.

H - 38 Neuropsychological Evaluation and Cognitive Profile of Stiff Person Syndrome (SPS) in a Predominantly Spanish-Speaking Older Adult: Is Cognition Really Affected?

Stiff Person Syndrome (SPS) is a rare autoimmune disorder that affects approximately one in every million people. It is characterized by progressive muscle rigidity and intense, episodic muscle spasms triggered by environmental and psychosocial (i.e., emotional stress) factors. While original diagnostic criteria for classical SPS included the absence of frank cognitive impairment (aside from what would be expected from seizures), more recent literature suggests a number of neurocognitive difficulties potentially associated with reduced GABA levels. The following case study presents a 73-year-old, predominantly Spanish-speaking man with 14years of education. His medical history is notable for over 20years with diagnosed SPS, hypertension well managed with medications, and the absence of other medical conditions that may contribute to cerebrovascular burden. He completed a comprehensive neuropsychological evaluation in Spanish. Overall, his profile was notable for mild inefficiencies in frontal-subcortical functions, with a relative weakness in rote learning and retention. He performed remarkably well relative to his level of motor compromise. There was no evidence of either a mild or major neurocognitive disorder, and his clinical interview and behavioral inventories were suspicious for a personality disorder. Recent literature proposes SPS is related to impairment in verbal learning, retention, fluency, processing speed, and attention. The present case corroborated, at most, mild inefficiencies in these previously documented areas. Careful consideration should be used in the evaluation of studies on SPS and cognition, particularly in determining whether samples had high degrees of comorbid conditions (i.e., cerebrovascular burden) that could help explain positive findings related to cognition.

AGR - 1 A Case Study of Cognitive Reserve and Wernicke's Aphasia Status-Post Insular Stroke.

The case is an 88-year-old, woman, formerly a successful surgeon for decades, with Wernicke's aphasia due to dominant insular stroke. Our evaluation explored her deficits in the context of the heterogeneous presentations of insular strokes and how speech rehabilitation has impacted her language abilities given her cognitive reserve prior to her stroke. The patient sustained a left MCA embolic stroke in 2020. Neurodiagnostics revealed an infarct in the insula, dominant temporal, frontal, and parietal lobes. Baseline language assessment was completed. Results included moderate-severe receptive language impairment; intact fluency; deficits in writing and repetition; and significant paraphasias. Neuropsychological assessment demonstrated prominent deficits in repetition with paraphasias and irritability. Auditory learning, attention, and working memory were invalid due to deficits in repetition. She was diagnosed with mild vascular neurocognitive disorder and conduction aphasia. Despite comprehension having improved, the patient's paraphasias resemble the presentation of Wernicke's aphasia. Interestingly, there were some consistencies in paraphasic errors, such as consistently swapping certain words or letters, demonstrating diminished but not absent volition of speech. Story memory was the most effective measure of auditory memory given repetition deficits. Despite repetition deficits commonly localizing to the supramarginal gyrus, her repetition difficulty is likely related to language network disruption due to her insular infarct. Rehabilitation for comprehension was successful despite age at time of injury. Consistent with previous research, results suggest despite cognitive reserve, repetition is resistant to rehabilitation; however, in this case, paraphasic errors were also resistant. Rehabilitation should include a behavioral component for insular stroke patients.